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An inhibitor of NAPE-PLD involved in lipid biosynthesis lowers levels of the endocannabinoid anandamide and other N-acylethanolamines in cells and mouse brain and activates the hypothalamus–pituitary–adrenal axis and impaired fear extinction.

Chemotherapy-induced peripheral neuropathy (CIPN) represents a major reason for discontinuation of treatment. Here, the authors show that LEI-515, a peripherally restricted monoacylglycerol lipase inhibitor, suppresses CIPN without inducing central nervous system side effects or physical dependence.

Global antibiotic scarcity looms owing to bacterial resistance. Now the discovery of a class of allosteric inhibitors targeting DNA gyrase—essential for bacteria—yields a compound LEI-800 that exhibits activity against fluoroquinolone-resistant E. coli. The compound’s unique mode of action, revealed through cryo-EM, makes it a promising candidate for countering bacterial resistance.

Mixed urinary incontinence troubles many patients worldwide but lacks effective therapies. Here, the authors present a wireless-powered soft bioelectronic implant to provide on-demand stimulation of the urethral sphincter, leading to improvement in both urge and stress urinary incontinence.

Cannabinoid CB₂ receptor (CB₂R) agonists are investigated as therapeutic agents in the clinic. Here, authors report the discovery of LEI-102, a CB₂R agonist, used in conjunction with three other CBR ligands (APD371, HU308, and CP55,940) to investigate selective CB₂R activation.

Many hospitalised children with acute illness in low- and middle-income countries experience incomplete recovery, readmission, and post-discharge mortality despite guideline-directed care. Here the authors report multiomic profiling to investigate biological drivers of hospital in-patient and post-discharge mortality in 3,101 acutely ill children across nine sites in sub-Saharan Africa and South Asia.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

High-latitude soils are future soil organic carbon loss hotspots, with losses dominated by particulate organic carbon (POC). The fraction of POC in total SOC (f_POC) is a key indicator, emphasizing the climate importance of preserving POC.

A tissue-clearing protocol integrated with mRNA and protein detection is applied to human bone to reveal quantitative differences in osteo-sinusoidal niches of human young and aged mesenchymal stromal cells.

N-desethyl-fluornitrazene is a µ-opioid receptor agonist derived from nitazenes that has supramaximal intrinsic efficacy that produces analgesia with minimal adverse effects in rodent models.

The electronic behaviour of complex oxides such as LaNiO₃ depends on many intrinsic and extrinsic factors, making it challenging to identify microscopic mechanisms. Here the authors demonstrate the influence of oxygen vacancies on the thickness-dependent metal-insulator transition of LaNiO₃ films.

Chen et al. engineer TRANSFER (trogocytosis-inspired receptor transfer and functional effector release), a method to deliver functional cargos from donor to recipient cells in a specific manner via direct cell–cell contact.

CREsted is an efficient and user-friendly toolbox for analysis, modeling and design of cell-type-specific enhancers across diverse species.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

Chen, Cai et al., present a rigorous human-in-the-loop framework for evaluating the medical performance of AI-generated responses to real clinical questions, using a scale aligned with physician career stages. Although some models perform at levels comparable to early-career physicians, substantial rates of incompetent answers and hallucinations demonstrate that unmonitored clinical deployment remains risky, underscoring the continuing need for expert oversight.

The authors mapped the continental-scale fraction of age-dependent leaf area index and revealed a widespread increase in the fraction of photosynthetically efficient young leaves across the majority of Amazon rainforests over the past decades.

Imprinting by influenza viruses can cause a deleterious shift of nearly the entire memory recall response against key, conserved epitopes.

The fluorescence-based protein assembly platform GEMINI is able to record the history of individual cells by leveraging a computationally designed protein assembly as an intracellular memory device.

Supersolid phases are quantum-entangled states of matter exhibiting the dual characteristics of superfluidity and solidity. Here, the authors map the phase diagram of K₂Co(SeO₃)₂. and identify signatures of two supersolid phases separated by a 1/3 magnetization plateau.

Selective C–H amination of electronically diverse (hetero)arene substrates is reported using an electrochemical strategy. Two convergent mechanistic pathways enable the tolerance of both electron-rich and electron-deficient (hetero)arenes. When electron-deficient substrates are used the process proceeds through electrophilic N-radical dicationic intermediates, following amine oxidation, whereas electron-rich substrates undergo arene oxidation.

Existing methods for the modification of exosomes adversely impact structures and functions of exosomal proteins and membranes. Here, the authors develop a chemically engineered platform by leveraging the synergistic interplay between CD38’s catalytic activity and the covalent inhibitor 2'-Cl-araNAD⁺.

The interface between LaAlO₃ and SrTiO₃ is host to exotic phenomena that can be controlled by light or electric fields. Lei et al. show that combining the two controls leads to a dramatic decrease, not increase, of carrier density at the heterointerface, beyond what can be done with only one of them.

Gu et al. introduce a cardiac foundation model that learns from millions of heart signals and textual interpretations, enabling it to handle heart data collected either in hospitals or at home. It offers clear and reliable insights across different devices and settings.

Nonlinear optical micropolarimetry and atomistic Monte Carlo simulations of monolayer NiPS₃ evidence a Berezinskii–Kosterlitz–Thouless phase that, with decreasing temperature, gives way to long-range order consistent with a six-state clock model.

Osteoporotic fractures are a major global health burden. Here the authors show, using proteome wide Mendelian randomization, that nine circulating proteins influence forearm fracture risk and identify a novel protective role for ephrin A1

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

In this study, long-read RNA sequencing achieves accurate single-nucleotide polymorphism calling, haplotype phasing and allele-specific expression analysis.

The study used snMultiome-seq to map gene expression and chromatin accessibility in human central amygdala cells from people with and without AUD. Here, the authors show that inhibitory neurons are most affected, with KLF16-driven regulatory changes and AUD-risk variants disrupting gene activity.

In this Review, Zhu et al. outline the various CRISPR-based tools recently built for dynamic DNA and RNA imaging, which have provided insights into various molecular mechanisms. The authors also discuss the important parameters to consider when using these tools, and how to approach the quantitative image analysis.

CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the adaptive immune response.

Liu et al. report Chinese normative lifespan brain charts showing later neurodevelopmental milestones than those detected in Western cohorts. Individual deviations from these norms are valuable in assessing clinical risk and outcomes.

The Assessing Genetic Diversity in Africa (AGenDA) project shares their processes, including community engagement, obtaining ethics approvals, navigating legal compliance and developing a common governance framework.

Confocal Airy beam integrated with single-photon oblique light-sheet tomography (CAB-OLST) is a high-throughput imaging approach for brain-wide mapping of neurons, as demonstrated in cleared mouse brains.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

The recently discovered kagome metal AV₃Sb₅ is a new playground to study the interplay between superconductivity and charge-density-wave (CDW) state. Here, the authors report pressure-dependent evolution of CDW and superconductivity in CsV₃Sb₅, suggesting an unusual competition between the two phases.